What are the other Names for this Condition? (Also known as/Synonyms)

• Faisalabad Histiocytosis and Sinus Histiocytosis with Massive Lymphadenopathy
• PHDIM Syndrome
• SLC29A3 Spectrum Disorder

What is Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus? (Definition/Background Information)

• Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus (PHDIM) is a rare genetic disorder characterized by the presence of excessive hair growth on the face, hands, and feet and the development of insulin-dependent diabetes mellitus. PHDIM is inherited in an autosomal recessive pattern
• This disorder is caused by mutations in the SLC29A3 gene, which leads to abnormal insulin regulation and abnormal hair growth. The risk factors for Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus include a positive family history of the disorder
• The most common signs and symptoms of Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus include overgrowth of hair on face, hands, and feet (not on the palms or soles), insulin-dependent diabetes mellitus, hyperglycemia, and glucose intolerance. PHDIM is typically diagnosed based on a combination of clinical examination, genetic testing, and blood glucose tests
• The treatment for Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus typically includes insulin therapy and blood glucose monitoring to control diabetes symptoms. Hair removal treatments may also be recommended to manage excessive hair growth. Currently, it is not possible to prevent PHDIM as it is a genetic condition 
• The prognosis for Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus varies from one individual to another and is dependent on its severity and treatment effectiveness. With proper management of the condition, most individuals can have an improved quality of life; although, if left untreated, it can lead to complications and reduced quality of life

Who gets Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus? (Age and Sex Distribution)

• Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus (PHDIM) is a rare disorder of unknown frequency
• PHDIM is present at birth (congenital manifestation); the onset of signs and symptoms occur during infancy
• It affects both males and females
• Even though ethnicity is not fully determined, many cases have been reported from the Middle East, India, Pakistan, Spain, and Bulgaria

What are the Risk Factors for Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus? (Predisposing Factors)

The risk factors for Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus include:

• Having a family history of the disorder
• Inheriting two copies of the mutated SLC29A3 gene, one from each parent, to develop the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others. 

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus? (Etiology)

• Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus is caused by mutations in the SLC29A3 gene, leading to abnormal insulin regulation and hair growth
• It is a genetic disorder that is inherited in an autosomal recessive manner

Autosomal recessive mode of inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus?

The signs and symptoms of Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus include:

• High fever with flares lasting longer than a week
• Psychomotor delays and impairment
• Excessive hair growth on the face, hands, and feet
• Insulin-dependent diabetes mellitus
• Hyperglycemia and glucose intolerance
• Eye involvement that includes uveitis and glaucoma causing vision loss and blindness
• Swollen or droopy eyelids
• Sensorineural deafness
• Short stature, dysmorphic facial features, rotated ears, macrocrania, pectus excavatum, wide-set nipples, short square hands, joint contractures
• Abdominal pain, diarrhea, and enlargement of the liver and/or spleen

How is Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus Diagnosed?

Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus is typically diagnosed based on a combination of the following:

• Clinical examination and medical history evaluation
• Assessment of the presenting signs and symptoms
• Blood glucose level measurements
• Imaging studies, as required
• Genetic testing

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus?

The complications of Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus may include:

• Excessive hair growth and other abnormalities leading to severe emotional and psychological distress
• Growth delay and short stature
• Deafness
• Blindness
• With febrile flares, pericarditis can develop
• Structural heart defects including ventricular septal defect (VSD), atrial septal defect (ASD), patent ductus arteriosus (PDA, mitral valve prolapse, and others
• Swollen lymph nodes and Rosai-Dorfman sinus histiocytosis with massive lymphadenopathy

How is Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus Treated?

• The treatment for Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus typically includes insulin therapy and blood glucose monitoring to control diabetes symptoms
• Hair removal treatments may also be recommended to manage excessive hair growth

How can Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus be Prevented?

• Currently, there are no known methods available to prevent Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus as the cause is a genetic mutation
• Genetic counselling and testing may be recommended for individuals with a family history of the disorder and for couples planning to have children

What is the Prognosis of Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus? (Outcomes/Resolutions)

The prognosis for Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus varies depending on the severity of the disorder and the effectiveness of the treatment.

• With proper treatment, most affected individuals can have a good quality of life
• Without adequate treatment, the disorder can cause significant complications and affect one’s overall quality of life

Additional and Relevant Useful Information for Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus:

The following link is a useful resource for further information on rare diseases and disorders:

https://www.dovemed.com/diseases-conditions/rare-disorders/