Dr. Mahak, Dr Sajitha Nair, Dr Sindhu, Dr Sreya, Dr Jayakumar, Department of Pediatrics, AIMS, Kochi
one year old male child, sixth child of third degree consanguinous marriage, born preterm at 35 weeks via Emergency LSCS(in view of PIH), developmentally normal and immunised for age presented with high grade intermittent fever of 3 week duration. No history of cough/weight loss/TB contact/vomiting/altered sensorium/crying while passing urine.
There was history of multiple episodes of febrile illnesses in the past requiring multiple hospital admissions.
Ba was noted to have hypopigmented hair since birth. No family history of similar depugmented hair present.
At 2 months old, ba was admitted for fever and found to be anemic. USG Abdomen- normal, spleen size 6.9cm.
At 4.5 months old, again admitted for similar complaints. Hb 8.4mg/dL.
At 6 months old, evaluated at Medical College for persistent anemia during another febrile episode.
Labs
TC 8.7K N24% Plt 300K Hb 9.4g% MCV 64
Sickling Test negative, Mentzer index 16, Retic Count 4.1%. Parents were advised regular follow up.
8.5 months- similar admission with. Hb of 10.2%
There was history of multiple intra-uterine deaths prior to the birth of this child
Ba had 2 elder siblings who were healthy females. Mother’s second pregnancy resulted in IUD near term. It was a male foetus. Third and fourth pregnancies also resulted in IUDs at 6 months. Both were female babies.
Clinical examination revealed pallor, silvery grey hair, eyelashes and eyebrows with brown iris. One cafe au lait macule was present on the back.
Auxology was within normal limits. Liver was palplable 1cm below the right costal margin with Liver Span of 8cm and the spleen was palpable 9cm below the Left Costal Margin. Other examination was normal.
Our differentials at this juncture with respect to this ba with hypopigmented hair were:
Chediak Higashi Syndrome
Griscelli Syndrome
Elejalde Syndrome
Hermansky Pudlack Syndrome
Labs showed neutropenia and microcytic anemia. TC 11.3 N 9.2% ANC 1043 L 89% Plt 94 Hb 7.5g% ESR 39 mm/hr
LFT/RFT/URE/Chest Xray/Blood Culture were normal.
Peripheral Smear showed microcytic hypochromic anemia with leukocytosis.
Dengue Panel/EBV IgM/CMV PCR/Immunoglobulin profile/ PreOp serology/2D Echo was also normal.
USG Abdomen showed splenomegaly 9.6cm.Lymphocyte sub set Panel showed CD8+ T cells and decrease in percentage and absolute count of CD4 + T cells.
Child developed worsening neutropenia and anemia with elevated Serum Ferritin (533ng/mL) and hypertriglyceridemia (776mg/dL), he was suspected to have HLH.
Bone Marrow Aspiration and Biopsy did not show hemophagocytosis. Normal trilinage maturation present. Normal Karyotyping present. No evidence of leukemia/lymphoma present on immunophenotyping.
Child was considered case of Hemophagocytic Lymphohistiocytosis with possibility of Griscelli Syndrome. WES was sent which proved the same.
Children with silvery grey hair should be evaluated with an algorithmic approach.
Chediak Higashi is a rare autosomal recessive disease with recurrent pyogenic infections, partial oculo cutaneous albinism and progressive neurologic abnormalities which occurs due to a defect in the LYST gene. HSCT is the treatment of choice.
Elejalde syndrome is also an autosomal recessive disorder characterised sivery grey hair, suntanned skin and severe neurologic dystfunction in the form of seizures, hypotonia and mental retardation.
Griscelli Syndrome is divided into 3 subtypes as described in the graphs.
Carry Home Message- Silvery Grey Hair must be evaluated.