A CASE REPORT ON FREQUENT FALLS – IS IT A METABOLIC  OR  A NUTRITIONAL  CAUSE ?


Dr.Venkatesh Kumar, Dr.Sheela Nampoothiri (Genetics),DrC Jayakumar
AIMS, Kochi.
Seven year old boy – first born of non-consanguineous marriage presented with difficulty in walking, frequent falls and abnormal walking pattern since 2 years of age. Our side AIMS hospital was investigated on so many occasions and surgery was advised after 15 years of age.He is immunised upto age and developmentally normal. 
His vitals were stable. 
Auxology 
Height of 103 cm(below 3rd centile) 
Weight of 16.2 kg(between 3rd and 10th centile).
He has waddling gait. 
Head to foot examination findings include large head,frontal bossing ,hyperelastic fingers, knock knees, sternal prominence, cubitus valgus, cafe-au-lait spot of 4×4 cm over left medial aspect of calf.
Systemic examination showed CNS findings
HMF-normal
Normal IQ
Cranial nerves-normal
Sensory Motor, Cerebellum were normal and no meningeal irritation.
Other systems were within normal limits.
Differential diagnosis considered were:
1. Rickets
2. Perthe’s disease
3. Spondyloepiphyseal dysplasia
4. Juvenile Idiopathic arthritis
5. Slipped capital femoral epiphysis (SCFE)

Investigations :
Hemogram: TC-10.60 ku/ml, N-36.2%, L-49.5%, E-8.7%, Hb-12.1 gm/dl, Plt- 228 ku/ml.
LFT: Total bilirubin- 0.79 mg/dl,Direct bilirubin- 0.23 gm/dl, SGOT- 24.8 IU/L, SGPT-12.2 IU/L,ALP-168 IU/L,Totalprotein- 6.7 gm/dl, S.Albumin-4.8 gm/dl.
RFT: Urea- 15.6 mg/dl,Creat- 0.25 mg/dl.
25-OH Vitamin D: 14.12 ng/dl (low).
Total calcium: 9.51 mg/dl
Serum phosphorous: 4.2 mg/dl
ECHO: Structurally normal heart.

Ophthalmology: Mild corneal clouding in both the eyes.

Lysosomal enzyme study from Leucocytes: revealed decreased levels of beta-galactosidase-6-sulphatase (Pt’s value-0.24), (Normal levels: 3 to 42.6 ) suggestive of Mucopolysaccharides-IV A / Morquio’s disease.
Impression: Mucopolysaccharides-IV A / Morquio’s diseasewith Vitamin-D deficiency.
Discussion:
Morquio’s disease is caused deficiency of N-acteylgalactosamine-6-sulphatase (gene encoding this enzyme is on chromosome 16) resulting in degradation of keratan sulfate.It has autosomal recessive inheritance.
Clinical features: Genu valgum, Kyphosis, Growth retardation with short trunk and neck, waddling gait with tendency to fall, extraskeletal manifestations- mild corneal clouding,small teeth with abnormally thin enamel,frequent caries formation,occasionally hepatomegaly and CVS lesions.Inabilityof odontoid process and ligamentous laxity is regularly present and can result in Atlantoaxial instability and life threateningdislocation.
Surgery to stabilize upper cervical spine before  development of cervical myelopathy can be lifesaving.
They are characterised short-trunk dwarfism, fine corneal deposits, skeletal dysplasia that is distinct from other mucopolysaccharidoses,preservation of intelligence.


MPS type IVA is more severe than MPS type IVB.
Diagnosis: Clinical suspicion of an MPS justifies skeletal survey.Radiographs of chest,spine,pelvis and skull mostly reveals features of of dystosis multiplex. 
Next diagnostic step is to assay urinary excretion of Glycosaminoglycans. 
Tandem massspectrometry is useful in diagnosis. 
Morquio’s disease is often missed in urinary assays but can be reliably diagnosed in serum using monoclonal antibodies to keratan sulfate.It should have definitive diagnosis established enzyme assay.Serum,Leukocytes or cultured fibroblasts are used as tissue source for measuring lysosomal enzymes.Prenatal diagnosis can be established cultured cells from amniotic fluid or chorionic villous biopsy.
Treatment: 
Elosulfase( Vimizim), symptomatic therapy.

Carry home message: Children presenting with complaints of frequent falls,abnormal walking pattern should not always be evaluated in aspect of Vit-D deficiency or any other neurological condition.It also needs extensive workup like those for mucopolysccharidosis like Lysosomal enzyme study there detecting the condition and improving the quality of life doing early intervention.