In addition to the symptoms associated with immunodeficiency, such as depletion of T-cells, decline of lymphocyte activity, and an abrupt proliferation of both benign and opportunistic infections — PNP-deficiency is often characterized by the development of autoimmune disorders. lupus erythematosus, autoimmune hemolytic anemia, and idiopathic thrombocytopenic purpura have been reported with PNP-deficiency.

Neurological symptoms, such as developmental decline, hypotonia, and mental retardation have also been reported.

Copper deficiency can cause a wide variety of neurological problems including, myelopathy, peripheral neuropathy, and optic neuropathy.

The characteristic hematological (blood) effects of copper deficiency are anemia (which may be microcytic, normocytic or macrocytic) and neutropenia. Thrombocytopenia (low blood platelets) is unusual.

The peripheral blood and bone marrow aspirate findings in copper deficiency can mimic myelodysplastic syndrome. Bone marrow aspirate in both conditions may show dysplasia of blood cell precursors and the presence of ring sideroblasts (erythroblasts containing multiple iron granules around the nucleus). Unlike most cases of myelodysplastic syndrome, the bone marrow aspirate in copper deficiency characteristically shows cytoplasmic vacuoles within red and white cell precursors, and karyotyping in cases of copper deficiency does not reveal cytogenetic features characteristic of myelodysplastic syndrome.

Anemia and neutropenia typically resolve within six weeks of copper replacement.

It is characterized by a lack of CD8+ T cells and the presence of circulating CD4+ T cells which are unresponsive to T-cell receptor (TCR)-mediated stimuli.

Fumarase deficiency causes encephalopathy, severe mental retardation, unusual facial features, brain malformation, and epileptic seizures due to an abnormally low amount of fumarase in cells. It can initially present with polyhydramnios on prenatal ultrasound. Affected neonates may demonstrate nonspecific signs of poor feeding and hypotonia. Laboratory findings in neonates may indicate polycythemia, leukopenia, or neutropenia. As they age, neurological deficits begin to manifest with seizures, dystonias, and severe developmental delay.

The signs and symptoms of DOCK8 deficiency are similar to the autosomal dominant form, STAT3 deficiency. However, in DOCK8 deficiency, there is no skeletal or connective tissue involvement, and affected individuals do not have the characteristic facial features of those with autosomal dominant hyper-IgE syndrome. DOCK8 deficient children often have eczema, respiratory and skin staphylococcus infections.

Beyond these, many other recurrent infections have been observed, including recurrent fungal infections and recurrent viral infections (including molluscum contagiosum, herpes simplex, and herpes zoster), recurrent upper respiratory infection (including "Streptococcus pneumoniae", "Haemophilus influenzae", respiratory syncytial virus, and adenovirus), recurrent sinusitis, recurrent otitis media, mastoiditis, pneumonia, bronchitis with bronchiectasis, osteomyelitis, candidiasis, meningitis (caused by cryptococcus or H. influenzae), pericarditis, salmonella enteritis, and giardiasis. Other dermatologic problems include squamous-cell carcinoma/dysplasia (vulvar, anal, and facial). Immune problems are also common, including autoimmune hemolytic anemia, severe allergies (both food and environmental), asthma, and reactive airway disease. The nervous system may also be affected; observed conditions in DOCK8 deficient people include hemiplegia, ischemic stroke, subarachnoid hemorrhage, and facial paralysis. Vascular complications are common, including aortic aneurysm, cerebral aneurysm, vessel occlusion and underperfusion, and leukocytoclastic vasculitis.

85–90% of IgA-deficient individuals are asymptomatic, although the reason for lack of symptoms is relatively unknown and continues to be a topic of interest and controversy. Some patients with IgA deficiency have a tendency to develop recurrent sinopulmonary infections, gastrointestinal infections and disorders, allergies, autoimmune conditions, and malignancies. These infections are generally mild and would not usually lead to an in-depth workup except when unusually frequent.

They may present with severe reactions including anaphylaxis to blood transfusions or intravenous immunoglobulin due to the presence of IgA in these blood products. Patients have an increased susceptibility to pneumonia and recurrent episodes of other respiratory infections and a higher risk of developing autoimmune diseases in middle age.

IgA deficiency and common variable immunodeficiency (CVID) feature similar B cell differentiation arrests, it does not present the same lymphocyte subpopulation abnormalities. IgA-deficient patients may progress to panhypogammaglobulinemia characteristic of CVID. Selective IgA and CVID are found in the same family.

Signs and symptoms of a biotinidase deficiency can appear several days after birth. These include seizures, hypotonia and muscle/limb weakness, ataxia, paresis, hearing loss, optic atrophy, skin rashes (including seborrheic dermatitis and psoriasis), and alopecia. If left untreated, the disorder can rapidly lead to coma and death.

Biotinidase deficiency can also appear later in life. This is referred to as "late-onset" biotinidase deficiency. The symptoms are similar, but perhaps more mild, because if an individual survives the neonatal period they likely have some residual activity of biotin-related enzymes. Studies have noted individuals who were asymptomatic until adolescence or early adulthood. One study pointed out that untreated individuals may not show symptoms until age 21. Furthermore, in rare cases, even individuals with profound deficiencies of biotinidase can be asymptomatic.

Symptom severity is predictably correlated with the severity of the enzyme defect. Profound biotinidase deficiency refers to situations where enzyme activity is 10% or less. Individuals with partial biotinidase deficiency may have enzyme activity of 10-30%.

Functionally, there is no significant difference between dietary biotin deficiency and genetic loss of biotin-related enzyme activity. In both cases, supplementation with biotin can often restore normal metabolic function and proper catabolism of leucine and isoleucine.

The symptoms of biotinidase deficiency (and dietary deficiency of biotin) can be quite severe. A 2004 case study from Metametrix detailed the effects of biotin deficiency, including aggression, cognitive delay, and reduced immune function.

Symptoms may differ greatly, as apparently modifiers control to some degree the amount of FX that is produced. Some affected individuals have few or no symptoms while others may experience life-threatening bleeding. Typically this bleeding disorder manifests itself as a tendency to easy bruising, nose bleeding, heavy and prolonged menstruation and bleeding during pregnancy and childbirth, and excessive bleeding after dental or surgical interventions. Newborns may bleed in the head, from the umbilicus, or excessively after circumcision. Other bleeding can be encountered in muscles or joints, brain, gut, or urine

While in congenital disease symptoms may be present at birth or show up later, in patients with acquired FX deficiency symptoms typically show up in later life.

Purine nucleoside phosphorylase deficiency, often called PNP-deficiency, is a rare autosomal recessive metabolic disorder which results in immunodeficiency.

Biotinidase deficiency is an autosomal recessive metabolic disorder in which biotin is not released from proteins in the diet during digestion or from normal protein turnover in the cell. This situation results in biotin deficiency.

Biotin, also called vitamin B, is an important water-soluble nutrient that aids in the metabolism of fats, carbohydrates, and proteins. Biotin deficiency can result in behavioral disorders, lack of coordination, learning disabilities and seizures. Biotin supplementation can alleviate and sometimes totally stop such symptoms.

No cure currently exists; however, gene therapy has been proposed.

Although MPO deficiency classically presents with immune deficiency (especially candida albicans infections), the majority of individuals with MPO deficiency show no signs of immunodeficiency.

The lack of severe symptoms suggest that role of myeloperoxidase in the immune response must be redundant to other mechanisms of intracellular killing of phagocytosed bacteria.

Patients with MPO deficiency have a respiratory burst with a normal nitro blue tetrazolium (NBT) test because they still have NADPH oxidase activity, but do not form bleach due to their lack of myeloperoxidase activity. This is in contrast to chronic granulomatous disease, in which the NBT test is 'negative' due to the lack of NADPH oxidase activity (positive test result means neutrophils turn blue, negative means nitroblue tetrazolium remains yellow).

Patients with MPO deficiency are at increased risk for systemic candidiasis.

Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is an autosomal recessive

metabolic disorder in which there is absent or significantly decreased activity of dihydropyrimidine dehydrogenase, an enzyme involved in the metabolism of uracil and thymine.

Individuals with this condition may develop life-threatening toxicity following exposure to 5-fluorouracil (5-FU), a chemotherapy drug that is used in the treatment of cancer. Beside 5-FU, widely prescribed oral fluoropyrimidine capecitabine (Xeloda) could put DPD-deficient patients at risk of experiencing severe or lethal toxicities as well.

Symptoms can be extremely varied among those suffering from pyruvate kinase deficiency. The majority of those suffering from the disease are detected at birth while some only present symptoms during times of great physiological stress such as pregnancy, or with acute illnesses (viral disorders). Symptoms are limited to or most severe during childhood. Among the symptoms of pyruvate kinase deficiency are:

- Mild to severe hemolytic Anemia

- Cholecystolithiasis

- Tachycardia

- Hemochromatosis

- Icteric sclera

- Splenomegaly

- Leg ulcers

- Jaundice

- Fatigue

- Shortness of breath

Myeloperoxidase deficiency is an autosomal recessive genetic disorder featuring deficiency, either in quantity or of function, of myeloperoxidase, an enzyme found in certain phagocytic immune cells, especially polymorphonuclear leukocytes.

It can appear similar to chronic granulomatous disease on some screening tests.

Signs of vitamin E deficiency include the following:

- Neuromuscular problems-such as spinocerebellar ataxia and myopathies.

- Neurological problems-may include dysarthria, absence of deep tendon reflexes, loss of the ability to sense vibration and detect where body parts are in three dimensional space, and positive Babinski sign.

- Hemolytic anemia-due to oxidative damage to red blood cells

- Retinopathy

- Impairment of the immune response

There is also some laboratory evidence that vitamin E deficiency can cause male infertility.

Tetrahydrobiopterin deficiency (THBD, BHD), also called THB or BH deficiency, is a rare metabolic disorder that increases the blood levels of phenylalanine. Phenylalanine is an amino acid obtained through the diet. It is found in all proteins and in some artificial sweeteners. If tetrahydrobiopterin deficiency is not treated, excess phenylalanine can build up to harmful levels in the body, causing intellectual disability and other serious health problems.

High levels of phenylalanine are present from infancy in people with untreated tetrahydrobiopterin (THB, BH) deficiency. The resulting signs and symptoms range from mild to severe. Mild complications may include temporary low muscle tone. Severe complications include intellectual disability, movement disorders, difficulty swallowing, seizures, behavioral problems, progressive problems with development, and an inability to control body temperature.

It was first characterized in 1975.

Vitamin E deficiency or hypovitaminosis E is a deficiency of vitamin E. It causes nerve problems due to poor conduction of electrical impulses along nerves due to changes in nerve membrane structure and function.

LRBA deficiency presents as a syndrome of autoimmunity, lymphoproliferation, and humoral immune deficiency. Predominant clinical problems include idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), and an autoimmune enteropathy. Before the discovery of these gene mutations, patients were diagnosed with common variable immune deficiency (CVID), which is characterized by low antibody levels and recurrent infections. Infections mostly affect the respiratory tract, as many patients suffer from chronic lung disease, pneumonias, and bronchiectasis. Lymphocytic interstitial lung disease (ILD) is also observed, which complicates breathing and leads to impairment of lung function and mortality. Infections can also occur at other sites, such as the eyes, skin and gastrointestinal tract. Many patients suffer from chronic diarrhea and inflammatory bowel disease. Other clinical features can include hepatosplenomegaly, reoccurring warts, growth retardation, allergic dermatitis, and arthritis. Notably, LRBA deficiency has also been associated with type 1 diabetes mellitus. There is significant clinical phenotypic overlap with disease caused by CTLA4 haploinsufficiency. Since LRBA loss results in a loss of CTLA4 protein, the immune dysregulation syndrome of LRBA deficient patients can be attributed to the secondary loss of CTLA4. Because the predominant features of the disease include autoantibody-mediated disease (AIHA, ITP), Treg defects (resembling those found in CTLA4 haploinsufficient patients), autoimmune infiltration (of non-lymphoid organs, also resembling that found in CTLA4 haploinsufficient patients), and enteropathy, the disease has been termed LATAIE for LRBA deficiency with autoantibodies, Treg defects, autoimmune infiltration, and enteropathy.

Factor X deficiency (X as Roman numeral ten) is a bleeding disorder characterized by a lack in the production of factor X (FX), an enzyme protein that causes blood to clot in the coagulation cascade. Produced in the liver FX when activated cleaves prothrombin to generate thrombin in the intrinsic pathway of coagulation. This process is vitamin K dependent and enhanced by activated factor V.

The condition may be inherited or, more commonly, acquired.

Selenium deficiency in combination with Coxsackievirus infection can lead to Keshan disease, which is potentially fatal. Selenium deficiency also contributes (along with iodine deficiency) to Kashin-Beck disease. The primary symptom of Keshan disease is myocardial necrosis, leading to weakening of the heart. Kashin-Beck disease results in atrophy, degeneration and necrosis of cartilage tissue. Keshan disease also makes the body more susceptible to illness caused by other nutritional, biochemical, or infectious diseases.

Selenium is also necessary for the conversion of the thyroid hormone thyroxine (T4) into its more active counterpart, triiodothyronine, and as such a deficiency can cause symptoms of hypothyroidism, including extreme fatigue, mental slowing, goiter, cretinism, and recurrent miscarriage.

Short-chain acyl-coenzyme A dehydrogenase deficiency affected infants will have vomiting, low blood sugar, a lack of energy (lethargy), poor feeding, and failure to gain weight and grow. Additional features of this disorder may include poor muscle tone (hypotonia), seizures, developmental delays, and microcephaly. The symptoms of short-chain acyl-CoA dehydrogenase deficiency may be triggered during illnesses such as viral infections. In some cases, signs and symptoms may not appear until adulthood, when some individuals may develop muscle weakness, while other individuals mild symptoms may never be diagnosed.

Loss of appetite and weight loss can occur. Additional signs are weakness, sore tongue, headaches, heart palpitations, irritability, and behavioral disorders. In adults, anemia (macrocytic, megaloblastic anemia) can be a sign of advanced folate deficiency.

Women with folate deficiency who become pregnant are more likely to give birth to low birth weight premature infants, and infants with neural tube defects. In infants and children, folate deficiency can lead to failure to thrive or slow growth rate, diarrhea, oral ulcers, megaloblastic anemia, neurological deterioration. Microcephaly, irritability, developmental delay, seizures, blindness and cerebellar ataxia can also be observed.

Fumarase deficiency (or fumaric aciduria), also known as "Polygamist Down's", is an autosomal recessive metabolic disorder in krebs cycle characterized by a deficiency of the enzyme fumarate hydratase, which causes a buildup of fumaric acid in the urine, and a deficiency of malate.