Case of DOCK8 deficiency

Dr.Ghaniya KC , DrSheela Nampoothiri DrSajith Keshavan Dr.Praveena N.Bhaskaran , Dr.Steffy Sunny , Dr.Navya George , Dr.Shela Sany ,DrC Jayakumar 

AIMS Kochi

Eleven year old girl child , presented with complaints of dry cough for 2 weeks , high grade intermittent fever, fast breathing and Chest retractions for 2 days.

She  had 3 episodes of Pneumonia  at 1 year, 3 years and 7 years of age and last admission  she was managed in an intensive care setup with (High frequency nasal cannula)HFNC .

Child was marasmic ,Pale  and Grade 3 clubbing was present.Patches of depigmentation and hyperpigmentation of arms and legs were also present.

 Fig 1 : Patches of depigmentation and hyperpigmentation of arms and legs were present.

  Fig 2 : 11 year old Child showing FTT.Wasting -3SD.Weight stunting-3SD . She was tachypneic , nasal flaring , use of accessory muscles and suprasternal retractions were present in addition to coarse crackles  in all lung fields.

DIFFERENTIAL DIAGNOSIS

Immunodeficiency 

Cystic fibrosis

Celiac disease with Diencephalic syndrome(neo plastic lesion of the hypothalamic -optic chasmatic region)

Structural lung malformations 

GER 

PCD 

Asthma 

Lab investigations done showed normal counts and elevated inflammatory markers CRP (35.85 mg/L).Chest X-ray showed B/l patchy infiltrates.TB-workup done and that was negative.Blood culture was negative.

Figure 3 : Chest X-ray showing B/L patchy infiltrates.

 Immunoglobulin profile showed low normal IgG and IgM , elevated levels of IgA and IgE.Flow cytometry showed reduced levels of CD3+ , CD8+ , CD19 + but normal absolute CD19+ levels..C3,C4 levels were  normal HRCT was suggestive of bronchiectasis.PFT done showed restrictive pattern. Sweat Chloride was 56 – indeterminate. Evaluation of FTT including TFT (normal)and X-ray left hand corresponded to a bone age of 3-4 years.Anti tTg A for celiac disease was negative .Ophthal evaluation to rule out diencephalic  syndrome  showed no papilledema.ECHO was  normal 

NBT – DHR was negative.

Genetic evaluation WES (Whole exome Sequencing) – DOCK8 mutation Hyper -IgE syndrome -2 with recurrent infections

Child was treated with IV Levofloxacin and nebulised bronchodilators for 9 days.Currently child is waiting for BMT.

DOCK-8 DEFICIENCY

• Dedicator of Cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency that exemplifies the broad clinical features of primary immunodeficiencies (PIDs), extending beyond recurrent infections to include atopy, autoimmunity and cancer.

• DOCK8 deficiency impairs immune cell migration, function and survival, and it impacts both innate and adaptive immune responses.

• Clinically, DOCK8 deficiency is characterized allergic inflammation as well as susceptibility towards infections, autoimmunity and malignancy.

TAKE HOME MESSAGE :

Hematopoietic stem cell transplantation (HSCT) is  the only curative treatment for DOCK8 deficiency, and is recommended based on the high morbidity and mortality associated with this disease

In recurrent pneumonia there is role for geneticists also.

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