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Alrich EM, Blank RH, Fomon JJ. Primary tumours of the small intestine. Am J Surg 1960; 99 : 33-39.

8. Bremer EH, Battaile WG, Bulle PH. Villous turnouts of the upper gastrointestinal tract. Clinical review and report of a case. Am J Gastroenterol 1968; 50 : 135-143.

9. Mirmadzlessi S, Farmer RG, Hawk WA. Villous tumours of the duodenum and

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10.

11.

jejunum. Report of four cases and review of literature. Am J Dig Dis 1973; 18 : 467- 476. Schulten MF, Oyasu R, Beal JM. Villous adenomas of the duodenum. A case report and review of literature. Am ] Surg 1976; 132 : 90-96. Gore L Williams WJ. Adenomatous polyp of the jejunum composed of gastric mucosa. Cancer 1953; 6 : 164-166.

Glycogen Storage Disease (Type-IV) with Cirrhosis and Metastatic Intrathoracic Neuroblastoma

A.K. Sarkar, S. Sarkar,* V. Asawa and A.K. Dutta Munshi**

Departments of Pediatrics, *Pathology and **Neuroradiology, Institute of Post Graduate

Medical Education and Research and S.S.K.M. Hospital, Calcutta

T he Glycogen storage diseases (GSD) or glycogenoses are a heterogenous group of inborn errors of carbohydrate metabolism that lead to storage of abnormal concentra- tions or structure of glycogen. Several well defined disorders of glycogen metabolism have been described based on the identi- fied enzymatic defects or sometimes the distinctive features. 1 Among different types of GSD, Type-IV is a rare disorder. Moreover, the association of intrathoracic neuroblastoma with wide spread metastases in a case of Type IV GSD with hepatic cirrhosis has not been documented yet and therefore deserves description.

CASE REPORT

A 9-month-old male, only child of non- consanguinous parents was admit ted in S.S.K.M. Hospital, Calcutta with progres-

sive distension of abdomen since the age of 2 months. Two weeks after admission the child developed suddenly a soft tissue swelling over the lower back followed by fever and respiratory distress a week later. There was no history of jaundice, convul- sion, flushing, excessive sweating or diar- rhea. Birth history was normal. Antenatal, natal and post natal periods were unevent- ful.

Physical examination revealed an anx- ious child with doll like facies having weight of 7 kg, length 67 cm skull circum- ference 40 cm and midarm circumference 12.5 cm. Respiration rate was 40/rain and BP 75/45 mm of Hg. Abdomen was dis- tended and showed presence of few prominent veins. No ascites was present. Liver was hugely enlarged, right lobe upto right iliac fossa and left lobe 4 cm in the epigastric area, very firm in consistency

294 THE INDIAN JOURNAL OF PEDIATRICS 1994; Vol. 61. No. 3

with sharp well defined margin, non ten- der and uneaven surface. The spleen was palpable 2 cm below the left costal margin. Examination of the respiratory system re- vealed dullness on percussion over the right upper zone with bronchial breath sounds and crepitations and ronchi on both sides of the chest. A soft tissue mass measuring 6 cm x 3 cm was present in the left paravertebral region at the level of lower thoracic spine. It was non tender, and not fixed to the deeper structures. Skin overlying the swelling was free. The rest of the systemic examination was non-con- tributory.

Investigative work up revealed moder- ate leukocytosis with a preponderance of polymorphonuclear cells, a normal platelet count and ADP aggregation test. Bone marrow aspirate showed at places rosette formation suggestive of neuroblastoma. Liver function tests revealed total bilirubin of 0.4 mg/d l , total protein of 6.3 g /d l with albumin 3 g/dl , alkaline phosphatase 180 IU/L, SGOT 34 IU/L, SGPT 30 IU/L and prothrombin time of 14.5 seconds against the control time of 12.5 seconds. Serum triglycerides were 100 mg/d l , cholesterol 132 mg /d l and lactic acid 12.8 mg/dl . Se- rum concentration of uric acid was normal. Random blood sugar was 96 mg/d l . The fasting blood sugar was 75 mg/d l and fol- lowing S/C injection of epinephrine its val- ues were 72 mg/d l , 69 mg/d l , 79 mg/d l , and 81 m g / d l when examined at 30 min- utes intervals for 2 hours. Post-prandial blood glucose was 96 mg/d l and 2 hours after epinephrine it became 93 mg/dl . HB s Ag was negative and alpha-fetoprotein 7.2 ng/ml (normal 0 - 10 ng/ml), 24 hours uri- nary VMA was 11.2 mg (normal 1-3 rag). ECG showed no abnormality. X-ray of

Fi 8. 1. C T scan of the abdomen showing enlarged liver with multiple irregular hypodense lesions and a soft tissue mass with dense calcification inside, involving the posterior mediastinum of left side.

chest (PA view) revealed a lower thoracic mass shadow, consolidation right upper zone with some amount of collapse and emphyse-matous changes left side. Lateral view confirmed the mass in the posterior mediast inum. Roentgeno grams of skull and long bones revealed no abnormality. Hepatic imaging with Tc 99 m - S - colloid showed multiple areas of diminished up- take. Spleen was enlarged with generally uniform uptake. Ultrasonography of abdo- men showed enlargement of both lobes of liver with multiple hyperechoic areas. Spleen was mildly enlarged but the kid- neys appeared normal. CT scan of abdo- men revealed liver was larger in size. There were multiple irregular hypodense lesion involving whole of liver paren- chyma (Figure 1). Spleen showed a mild enlargement, but of normal shape. 13oth kidneys revealed no significant abnormali- ties with pelvi-calyceal pattern. There was evidence of a soft tissue mass with dense

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Fig. 2. The section of liver showing vacuolated l~ep'a tocytes forming mosaic pattern (straight arrows) and fibrous band traversing the liver parenchyma forming pseudolobule (curved arrows). (H x E x 80).

Fig. 3. The high power view of the secondary deposit of neuroblastoma showing rosette formation (arrow head). (H x E x 320).

calcification inside (H31HU) involving the posterior mediastinum of left side, and ret- roperitoneal region upto upper pole of left kidney. There was pleural reaction on the left side. Liver biopsy revealed distended hepatocytes with clear cytoplasm contain- ing glycogen with mosaic pattern sepa- rated by fibrous bands. These clear spaces were PAS-positive diastase-resistant. There was also pseudolobule formation in the area (Figure 2). In other areas there was a malignant tumor composed of small dark round and spindle shaped cells forming rosettes (Figure 3). The histological fea- tures were suggestive of GSD with cirrho- sis, and a malignant tumor probably a hepatoblastoma or neuroblastoma. Biopsy of subcutaneous mass showed features of neuroblastoma.

The patient was treated for right sided pneumonic consolidation with a course of broad spectrum antibiotics with gratifying result and subsequently with vincristine, cytoxan and doxorubicin and showed

some clinical improvement. Unfortunately he was taken back home by the parents on their own accord a few days after initiation of cancer chemotherapy, and could not be followed up further.

DIscussioN

Gradual abdominal distension from early infancy, huge hepatomegaly and mild splenomegaly is indicative of a metabolic disorder which has probably given rise to cirrhosis.It needs to be emphasized that most cases of GSD are characterized by huge hepatomegaly without any splenomegaly unless portal hypertension supervenes due to cirrhosis. 2 In type III GSD there is portal fibrosis which may lead to portal hypertension. Hepatic Cir- rhosis is not a common feature as the fi- brous septa usually remain stable.' Pro- gressive portal fibrosis, cirrhosis, portal hypertension and liver failure are the hall marks of Type IV disease? There have

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been only isolated case reports of GSD from India, ~-* but the disorder shall be kept in mind especially where there is family history of a similar disorder or where pa- rental consanguinity exists.

Due to lack of facilities for specific enzy- matic study it is rather difficult to precisely categorise our patient, but an attempt has been made to classify the case on the basis of clinical and biochemical findings. Ab- sence of hypoglycemia, lactic acidosis, hyperlipidemia, bleeding diathesis, renal enlargement and presence of normal plate- let adhesiveness s may be important point- ers against diagnosis of Type I GSD. Fail- ure of rise of blood glucose with S/C epi- nephrine administered 2 hours after a meal, and normal serum transaminase lev- els excludes Type III GSD. In GSD Type VI due to liver phospharylase deficiency, of- ten there is no hyperglycaemic reaction to glucagon/epinephrine. In addition, both cirrhosis with esophageal varices and liver adenomas and malignant tumor have been reported in GSD Type VI. 6 However, in this condition there may be some elevation of serum lipids and transaminases. 1 More- over glycogen being of normal structure is not diastase resistant. Additionally malig- nant tumor if associated with this condi- tion is always pr imary in nature and not metastatic. Some patients with GSD Type VI have subtle and unexplained cardiomyopathy. I Taking all these facts into consideration a diagnosis of GSD Type IV with hepatic cirrhosis was made which could only be confirmed by "brancher" enzyme assay or demonstrat- ing the typical structure of the abnormal glycogen ultrastructurally.

In Type IV GSD, liver glycogen is abnor- mal in structure and stains in an abnormal fashion intracytoplasmic globules are

present which stain positively with PAS as does normal glycogen, but are resistant to digestion with diastase. These may re- semble PAS - positive diastase-resistant intracytoplasmic inclusions of alphaantitrypsin (a 1 - AT) but marked dis- tension of liver cells and wide spread accu- mulation of intracy-toplasmic material giv- ing mosaic pattern is suggestive of Type IV GSD rather than that of a,-AT where the inclusions are seen mainly in periportal hepatocytes though specific immunofluo- rescent staining is more of diagnostic value, r Moreover, cirrhosis in a 1 - AT deft- ciency is usually a feature later in the first decade or during adolescence, and rather unknown in infancy.

Moreover our patient was also suffering from neuroblastoma and curiously enough hepatic involvement in this case was not associated with pr imary tumor in the ab- domen. Here metastases in liver, skin and bone mar row had occured from an asymptomatic intrathoracic growth. Neu- roblastoma is considered to be the most common malignant abdominal tumor found in infancy and childhood, but owing to it's origin from neural crest tissue it pre- sents with a wide spectrum of sign and symptoms. 8

As per staging systems currently in use for neuroblastoma, our patient may conve- niently be placed in stage IVS (Evans stages) where the pr imary lesion is small or unidentified and remote involvement is confined to liver skin or bone marrow (not bones). Almost all such patients are trader 6 months of age at the onset. 9 It is reported that patients with Von Gierke disease have been an increased incidence of hepatoma, 1 but secondaries in liver from neuroblas- toma as found in the present case is noth- ing unusual and probably related to the

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same way the affinity of this malignant neoplasm to involve liver and other tissues in situations where there are no inborn er- ror of metabolism.

REFERENCES

1. George H. Defects in Metabolism of carbohydrates. In : Behrman RE, Kliegman RM, Nelson WE, Vaughan VC, eds. Nelson's Textbook of Pediatrics, 14th edn, Philadelphia : W.B. Saunders, 1992 : 359-372.

2. Singh M, Fazal MI, Tana Iet al. Glycogen storage disease. Indian Pediatr 1983; 20 : 208-212.

3. Kalra V, Arya LS, Nayak NC. Glycogen storage disease (Type IV) : A familial cirrhosis diagnosed by electron microscopy. Indian Pediatr 1980; 17 : 625- 627.

4. Sarkar AK, Ghosh T, Chowdhury et al. Glycogen storage disease (Type III).

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Indian Pediatr 1991; 28 : 1058-1061. 5. Czapek EE, Deykin D, Salzman EW.

Platelet dysfunction in glycogen storage disease Type I. Blood 1973; 41 : 235-247.

6. Hers HG, Von Hoof F, De Barsy T. Glycogen storage disease In : Seriver CR, Beaudet AL, Sly WS, Valle D, eds, The Metabolic Basis of Inherited Disease, Vol I, 6th edn., New York :Mc Graw-Hill, 1989 : 425-452.

7. Tarlow McT. Glycogen storage disease. In : Chandra RK, ed, The Liver and Biliary System in Infants and Children, Edinburgh: Churchill Livingstone, 1979 : 210-213.

8. Kulshrestha R, Mohan M, Chawla D et al. Unusual presentation of neuroblastma. Indian Pediatr 1983; 20 : 204-208.

9. Leventhal BG. Neoplasms and neoplasm- like structures. In : Behrman RE, Vaughan VC, Nelson WE, eds. Nelson's Text Book of Pediatrics, 13th edn. Phila.delphia : W.B. Saunders Co. 1987 : 1079-1110.

Multiple Sclerosis in Childhood

Eray Dirik, Alp Sen, Ismet Dural(,* Mehmet Ergin*

Faculty of Medicine, Departments of Pediatrics and *Ophthalmology, Dokuz Eyliil University,

35340 InciraItL Izmir-Tiirkiye

Mul t ip l e sclerosis (MS) is a demyelinating disease of the central nervous system that is rarely seen in children. Only 2 % of all patients with MS experience onset in child- hood. ~

Ataxia, concurrent with a febrile epi- sode, is the most common initial presenta- tion in children. Optic neuritis, vertigo, headaches, somnolence, tlnnltus, hearing loss and sphincter incompetence are the

other clinical features. 2 MS in early child- hood may present atypically, with a symptomato logy suggesting diffuse encephalomyelitis, meningeal reaction, brain edema and seizures. 3 In diagnosis of multiple sclerosis, the most helpful proce- dures are cerebrospinal fluid examination, computed tomography, magnetic reso- nance imaging and electrophysiologic studies. ~-2